Ceramide production enhancer and moisturizer

ABSTRACT

A ceramide production enhancer and a moisturizer containing, as an active ingredient, an extract of at least one plant selected from the group consisting of  Chenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsium japonicum, Catalpa ovate , and  Tagetes erecta , or a compound represented by the following Formula (1): 
     
       
         
         
             
             
         
       
         
         
           
             wherein, R represents an acyl group having 1 to 5 carbon atom(s).

TECHNICAL FIELD

The present invention relates to a ceramide production enhancer and amoisturizer.

BACKGROUND ART

Although ceramides, which are one class of sphingolipids, are lipidsthat are available only in an extremely small amount with respect to thewhole body, in the stratum corneum which is the outermost layer of theskin, ceramides are contained more than half of the amount of lipids,and play the important roles in the water holding function and barrierfunction of the skin. These ceramides are produced in the epidermalcells, then secreted to form a lamellar structure in intercellularspaces of the stratum corneum, and they maintain the stratum corneumfunctions. It has been extensively reported that, in skin diseases suchas dry skin, rough skin, atopic dermatitis, senile xerosis andpsoriasis, normal metabolism of ceramides is interfered and the amountof ceramides in the stratum corneum decreases, followed by occurringdeterioration of the water holding function, barrier function and thelike of the skin.

There have been attempts to develop methods of supplying decreasedceramides from an external source, but at present, the effects of themethods are not necessarily sufficient.

SUMMARY OF INVENTION

The present invention is contemplated for providing a ceramideproduction enhancer having an effect of enhancing ceramide production ata higher level. Further, the present invention is contemplated forproviding a moisturizer excellent in a function to enhance ceramideproduction.

In view of the purposes described above, the inventors of the presentinvention have made extensive studies. As a result, they have found outthat plant extracts of Chenopodium hybridum, Melia toosendan, Indigoferatinctoria, Cirsium japonicum, Catalpa ovata and Tagetes erecta have afunction to enhance ceramide production at a higher level.

Further, the inventors of the present invention found out that acompound represented by the following Formula (1) has a function toenhance ceramide production at a higher level, and obtained a findingthat this compound is useful as a novel moisture-retaining component.The present invention has been completed based on these findings.

The present invention provides the following means:

(1) A ceramide production enhancer, containing an extract of at leastone plant selected from the group consisting of Chenopodium hybridum,Melia toosendan, Indigofera tinctoria, Cirsium japonicum, Catalpa ovataand Tagetes erecta as an active ingredient.

(2) A moisturizer, containing an extract of at least one plant selectedfrom the group consisting of Chenopodium hybridum, Melia toosendan,Indigofera tinctoria, Cirsium japonicum, Catalpa ovata and Tageteserecta as an active ingredient.

(3) A ceramide production enhancer, containing a compound represented bythe following Formula (1) as an active ingredient:

wherein R represents an acyl group having 1 to 5 carbon atom(s).

(4) A moisturizer, containing the compound represented by the aboveFormula (1) as an active ingredient.

(5) An extract of at least one plant selected from the group consistingof Chenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata and Tagetes erecta for use in the enhancementof ceramide production.

(6) An extract of at least one plant selected from the group consistingof Chenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata and Tagetes erecta for use in the moistureretention.

(7) The compound represented by the above Formula (1) for use in theenhancement of ceramide production.

(8) The compound represented by the above Formula (1) for use in themoisture retention.

(9) A method of enhancing ceramide production, including applying anextract of at least one plant selected from the group consisting ofChenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata and Tagetes erecta to a skin.(10) A method of retaining moisture, including applying an extract of atleast one plant selected from the group consisting of Chenopodiumhybridum, Melia toosendan, Indigofera tinctoria, Cirsium japonicum,Catalpa ovata and Tagetes erecta to a skin.(11) A method of enhancing ceramide production, including applying thecompound represented by the above Formula (1) to a skin.(12) A method of retaining moisture, including applying the compoundrepresented by the above Formula (1) to a skin.(13) Use of an extract of at least one plant selected from the groupconsisting of Chenopodium hybridum, Melia toosendan, Indigoferatinctoria, Cirsium japonicum, Catalpa ovata and Tagetes erecta for thepreparation of a medicament having an effect of retaining moisture basedon enhancing ceramide production.(14) Use of the compound represented by the above Formula (1) for thepreparation of a medicament having an effect of retaining moisture basedon enhancing ceramide production.

According to the present invention, a ceramide production enhancer canbe provided. Further, according to the present invention, a moisturizerexcellent in a function to enhance ceramide production can be provided.

Other and further features and advantages of the present invention willappear more fully from the following description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram showing the amounts of ceramides when using theextracts of Chenopodium hybridum, Melia toosendan, Indigofera tinctoria,Cirsium japonicum, Catalpa ovata, and Tagetes erecta.

MODE FOR CARRYING OUT INVENTION

Hereinafter, the present invention is described in detail.

The ceramide production enhancer and the moisturizer of the presentinvention contain, as an active ingredient, an extract of at least oneplant selected from the group consisting of Chenopodium hybridum, Meliatoosendan, Indigofera tinctoria, Cirsium japonicum, Catalpa ovata andTagetes erecta, or the compound represented by the above Formula (1).The extract and the compound have a function to enhance ceramideproduction at a higher level.

First, the ceramide production enhancer and the moisturizer of thepresent invention, both of which contain plant extracts as activeingredients, are explained.

According to the present invention, Chenopodium hybridum is a plantwhich belongs to the family Rubiaceae, genus Chenopodium. This plant hasbeen traditionally used as a dye, and in addition to that, as medicinaleffects of this plant, a sendative action has been known.

Melia toosendan is a plant which belongs to the family Meliaceae, genusMelia, As medicinal effects of this plant, a sedative action, ananalgesic action and an anthelmintic action have been known.Furthermore, a dried fruit of Melia toosendan has been used as an herbalmedicine called Senrenshi.

Indigofera tinctoria (alias: Nanbanai) is a plant which belongs to thefamily Polygonaceae, genus Indigofera. This plant has been traditionallyused as a dye or a pigment, and a product obtained by drying the pigmentpresent in the leaves is called Seitai.

Cirsium japonicum is a plant which belongs to the family Asteraceae,genus Cirsium. As medicinal effects of this plant, a diuretic action, aneuralgia-relieving action and the like have been known. A dried root ofthis plant is used as an herbal medicine called Taikei.

Catalpa ovate is a plant which belongs to the family Bignoniaceae, genusCatalpa. As a medicinal effect of this plant, a diuretic action has beenknown. A dried fruit of this plant is called Shijitsu, and has been usedas an herbal medicine.

Tagetes erecta (alias: Senju chrysanthemum) is a plant which belongs tothe family Asteraceae, genus Tagetes. As medicinal effects of thisplant, an eye disease preventive action and an eyestrain-relievingaction have been known.

With respect to Chenopodium hybridum, Melia toosendan, Indigoferatinctoria, Cirsium japonicum, Catalpa ovata, and Tagetes erecta used inthe present invention, any and all parts of the plant can be used. Forexample, any one or more selected from whole tree of the plant, wholegrass of the plant, or any part (roots, rhizomes, trunks, branches,stems, leaves, barks, tree sap, tree resin, flowers, fruits, seeds,pericarp, shell, germ, spike, heartwood, and the like), and combinationsthereof, can be used.

In the present invention, among the various parts of the plantsmentioned above, it is preferable to obtain an extract particularly fromthe parts described below.

In order to obtain an extract of Chenopodium hybridum, it is preferableto extract the whole grass of Chenopodium hybridum.

In order to obtain an extract of Melia toosendan, it is preferable toextract the fruits of Melia toosendan. Further, in the case ofextracting the fruits of Melia toosendan, Senrenshi, which has been usedas an herbal medicine, can be used.

In order to obtain an extract of Indigofera tinctoria, it is preferableto extract the leaves of Indigofera tinctoria, and it is also preferableto use the pigment obtained from the leaves of Indigofera tinctoria.

In order to obtain an extract of Cirsium japonicum, it is preferable toextract the roots of Cirsium japonicum. Further, in the case ofextracting the roots of Cirsium japonicum, Taikei, which has been usedas an herbal medicine, can be used.

In order to obtain an extract of Catalpa ovata, it is preferable toextract the fruits of Catalpa ovata. Further, in the case of extractingthe fruits of Catalpa ovata, Shijitsu, which has been used as an herbalmedicine, can be used.

In order to obtain an extract of Tagetes erecta, it is preferable toextract the flowers of Tagetes erecta.

There is no particular limitation on the method for preparing extractsof Chenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata and Tagetes erecta that are used in the presentinvention, and extracts can be obtained by extracting the plants byconventional methods. Specifically, juice extracts obtained by pressedextraction of dried products prepared by drying the plants describedabove or ground products thereof and the like; steam distillates; crudeextracts obtained by using various extraction solvents; fractions of theextracts obtained by purifying the crude extracts using variouschromatographic techniques such as partition chromatography and columnchromatography; and the like can be used as the extracts of the presentinvention.

The plants described above can be supplied to the extraction process inan unprocessed state, but in order to enhance the extraction efficiency,it is also preferable to apply processes such as drying, fine cuttingand grinding. Also, in the present invention, the extracts, steamdistillates, pressed products and the like described above may be usedsuch that any one of them is used alone, or two or more kinds are usedin combination. Among them, as the plant extract of the presentinvention, it is more preferable to use an extract obtained from a driedproduct prepared by drying the plants, or a ground product thereof, byusing an extraction solvent.

As the extraction solvent, any of polar solvents and non-polar solventscan be used, and mixtures of these solvents can also be used. Examplesinclude water; alcohols such as methanol, ethanol, propanol and butanol;polyhydric alcohols such as ethylene glycol, propylene glycol, andbutylene glycol; ketones such as acetone and methyl ethyl ketone; esterssuch as methyl acetate and ethyl acetate; linear and cyclic ethers suchas tetrahydrofuran and diethyl ether; polyethers such as polyethyleneglycol; halogenated hydrocarbons such as dichloromethane, chloroform,and carbon tetrachloride; hydrocarbons such as hexane, cyclohexane andpetroleum ether; aromatic hydrocarbons such as benzene and toluene;pyridines; supercritical carbon dioxide; oils and fats, waxes, and otheroils. Alternatively, a mixture combining two or more kinds of thesolvents described above can be used as the extraction solvent. Amongthese, it is preferable to use water, an alcohol, a water-alcohol mixedliquid, propylene glycol, or butylene glycol, and it is more preferableto use an aqueous ethanol solution.

The extraction conditions for obtaining the extract used in the presentinvention may vary depending on the solvent used, and thus, there are noparticular limitations. For example, when extraction is carried outusing water, an alcohol, a water-alcohol mixed liquid, propylene glycolor butylene glycol, it is preferable to subject the plant to immersionor heating to reflux, preferably using 1 to 50 parts by volume of asolvent relative to 1 part by mass of the plant, preferably at atemperature of 3° C. to 100° C., and more preferably 20° C. to 80° C.,preferably for one hour to several weeks, and more preferably for 1 dayto 30 days. Further, in order to enhance the extraction efficiency,stirring may be performed in addition, or a homogenization treatment maybe carried out in a solvent.

Although the extract obtained by performing extraction with the abovesolvent may be directly used; a fraction having higher activity obtainedby further fractionating the extract by an appropriate separatingtechnique such as gel filtration, chromatography or precisiondistillation can also be used. In the present invention, the term plantextract encompasses various extracts obtained by the methods describedabove diluted solutions thereof, concentrated solutions thereof,purified products thereof, and dried powders of these extracts.

Further, in the ceramide production enhancer or moisturizer of thepresent invention, the extract of each plant described above may be usedsingly, and also, the mixture of two or more kinds of the extracts maybe used.

The plant extracts obtained from Chenopodium hybridum, Melia toosendan,Indigofera tinctoria, Cirsium japonicum, Catalpa ovate, and Tageteserecta (hereinafter, also called plant extracts of the presentinvention) have an excellent function to enhance ceramide production asshown in the Examples described below, and a ceramide productionenhancer can be obtained by incorporating these extracts therein.Further, since ceramides play an important role in the water holdingfunction or barrier function of the skin as described above, when theceramide production is enhanced, the ceramide production mechanism ofthe organism may be returned to normal, the decreased level of ceramidesin the stratum corneum may be increased, and a skin having a highbarrier function and a high water holding function may be recovered.Therefore, a moisturizer can be obtained by incorporating the plantextracts described above therein.

Furthermore, in recent years, it has been reported that when theproduction of ceramides in the cells is enhanced, phenomena such asapoptosis, differentiation, and suppression of proliferation areinduced. Thus, attention is paid to ceramides as intracellular signalingmolecules that control the proliferation, differentiation, apoptosis andthe like of cells (see, for example, Sphingolipid targets in cancertherapy, David E. Mordrak, et al., Molecular Cancer Therapeutics, 20065(2):pp. 200-8). From these, it can be contemplated that a substancewhich enhances the production of ceramides can be expected to have aneffect of preventing/improving inflammatory diseases and diseasesattributable to abnormal proliferation or differentiation of cells, suchas malignant tumors, through the suppression of proliferation, inductionof differentiation, induction of apoptosis and the like in animal cells.Further, ceramides have a bone resorption inhibitory function, a bonestrengthening function, and an alveolar bone loss inhibitory function,and it has also been reported that ceramides are useful for theprevention and improvement of bone and joint diseases such asosteoporosis, bone fracture, lumbago and rheumatism (see, for example,JP-A No. 2001-158736), are effective in the prevention of periodontaldiseases (see, for example, JP-A No. 2001-158735), and have an functionto impart tension and resilience to hair and improving the feel to touch(see, for example, JP-A No. 10-152421). Therefore, the plant extract ofthe present invention is also useful for the use in medicines andcosmetic materials intended for the suppression of the proliferation oractivation of cancer cells, an enhancement of tension and resilience ofhair, the prevention and improvement of bone and joint diseases, and thelike.

It has not been known hitherto that plant extracts obtained fromChenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata, and Tagetes erecta have a function to enhanceceramide production at all, and this is a new discovery found by theinventors of the present invention.

In the present invention, the plant extract of the present inventionobtained from the plants described above may be directly used as aceramide production enhancer. Alternatively, various additives may beadded to the plant extract to the extent that the effects of the plantextract are not affected. For example, appropriate liquid or solidexcipients or bulking agents such as titanium oxide, calcium carbonate,distilled water, lactose and starch, may be added to the plant extract,and the resulting mixture may be used as the ceramide productionenhancer.

In the case of preparing a composition, the amount of the plant extractin the ceramide production enhancer is not particularly limited, but itis preferable that the extract be contained in an amount of 0.00001% to20% by mass, and particularly preferably about 0.0001% to 10% by mass,in terms of the solids content.

In the present invention, the extract obtained from the plants describedabove may be directly used as a moisturizer. Alternatively, the plantextract is incorporated as an active ingredient, and conventionally usedadditives, other efficacious ingredients and the like are alsoincorporated to the extent that the effects of the plant extract is notaffected, to prepare the moisturizer. For example, a ceramide productionenhancer that is already known, a pseudo-ceramide, a natural ceramide, aceramide saccharide and the like may be incorporated together.Furthermore, an anti-skin aging agent, a whitening agent and the likemay be added together as the efficacious ingredients in addition to theingredients having moisturizing effects.

There are no particular limitations on the ceramide production enhanceralready known, but examples include acetylhydroxyproline, potassiumglycyrrhizinate, L-camitine, ascorbic acid, ascorbyl glucoside,magnesium ascorbyl phosphate, dl-α-tocopheryl-dl-ascorbyl phosphate,dl-α-tocopheryl phosphate, nicotinic-acid amide, tocopherol nicotinate,L-lactic acid, vitamin C, asparagus extract, Butcher's broom, genkwanin,rosemary, lavender, sage, jujube, black (red) reishi, angelica root,sophora root, coix seed, venetian extract, and rice power extract.

Furthermore, there are no particular limitations on the pseudo-ceramide,but examples include commercially available Ceramide R (manufactured byUnilever PLC), Ceramide PC-104 (manufactured by Amorepacific Corp.),Ceramide HO3 (manufactured by Sederma GmbH), Eldew PS-203 (manufacturedby Ajinomoto Co., Inc.), and Sphingolipid E (manufactured by Kao Corp.).

Furthermore, there are no particular limitations on the ceramidesaccharide, but examples include glucosylceramide andgalactosylceramide, while commercially available examples include NippnCeramide (manufactured by Nippon Flour Mills Co., Ltd.), Oryza Ceramide(manufactured by Oryza Oil & Fat Chemical Co., Ltd.), Nissan Ceramide,Neoliquid Ceramide N (manufactured by NOF Corp.), and Ceramide(manufactured by Unitika, Ltd.).

In the case of preparing a composition, the amount of the plant extractin the moisturizer is not particularly limited, but it is preferablethat the extract be contained in an amount of 0.00001% to 20% by mass,and more preferably 0.0001% to 10% by mass; in terms of solids content.

Next, a ceramide production enhancer and a moisturizer containing acompound represented by the following Formula (1) as an activeingredient are explained below.

In Formula (1), R represents an acyl group having 1 to 5 carbon atom(s).

R is preferably an acyl group having 1 to 3 carbon atom(s), and morepreferably an acyl group having two carbon atoms. Specific examples of Rinclude a formyl group, an acetyl group, a propionyl group, a butyrylgroup, an isobutyryl group, a valeryl group and an isovaleryl group.Among them, a formyl group, an acetyl group, and a propionyl group arepreferred, and an acetyl group is more preferred. A compound representedby the Formula (1) in which R is an acetyl group is toosendanin, whichis a kind of terpene.

The compound represented by the Formula (1) may adopt tautomeric formsas shown below, and the compound represented by the Formula (1) of thepresent invention encompasses both of the tautomers.

The method for producing the compound represented by the above Formula(1) used in the present invention is not particularly limited. Achemically synthesized compound may be used, and a compound extracted orpurified from a natural product-derived material may also be used.Furthermore, a product that is commercially available as a reagent canalso be used.

As the reagent, a product commercially available from Avachem ScientificLLC (USA) and the like can be used.

With regard to the method of obtaining the compound represented by theabove Formula (1) from a natural product-derived material, for example,the compound can be isolated from plants such as Melia toosendan Sieb.et Zucc., Melia azedarach, and Toona sinensis.

For these plants, any and all parts (whole tree, whole grass, roots,rhizomes, trunks, branches, stems, leaves, barks, tree sap, tree resin,flowers, fruits, seeds and the like of the plant) can be used.Particularly, in the case of isolating the compound from Melia toosendanSieb. et Zucc., it is preferable to use the barks, seeds or fruits ofthe plant. Further, an herbal medicine obtained by using the fruits ofMelia toosendan Sieb. et Zucc. as the original plant, Senrenshi, canalso be used. In the case of isolating the compound from Meliaazedarach, it is preferable to use the barks of the plant. An herbalmedicine obtained by using the barks of Melia azedarach as the originalplant, Kurenpi, can also be used. In the case of isolating the compoundfrom Toona sinensis, it is preferable to use the barks of the plant.

The compound represented by the Formula (1) can also be isolated byusing these various plants or various parts in appropriate combination.

The method of isolating the compound represented by the above Formula(1) from these plants is not particularly limited, but an example may bea method in which the plant mentioned above is applied to the extractionusing an appropriate solvent, and isolating the compound represented bythe above Formula (1) from the obtained plant extract by using atechnique such as chromatography.

The plant can be used directly or after drying and grinding, for thepreparation of the plant extract. As a solvent that is used for theextraction, those conventionally used for the extraction of plantcomponents, for example, water, petroleum ether, n-hexane, toluene,chloroform, ether, ethyl acetate, acetone, methanol, ethanol, propanol,butanol, ethylene glycol, propylene glycol, butylene glycol and mixedsolutions thereof, can be used. Further, with regard to the extractioncondition, typical extraction conditions can be employed. For example,the above-described plant may be dipped or heated under reflux for twohours to 60 days at 5 to 80° C.

Specific methods for extraction and isolation that can be used includethe methods shown in the following Examples, but the present inventionis not limited thereto.

The compound represented by the above Formula (1) has an excellentfunction to enhance ceramide production as shown in the followingExamples, and a ceramide production enhancer can be obtained byincorporating this compound therein. Further, as described above, sinceceramides have an important function in the moisturizing mechanism orbarrier mechanism of the skin, when the ceramide production is enhanced,the ceramide production mechanism of the organism may be returned tonormal, the decreased level of ceramides in the stratum corneum may beincreased, and a skin having a high barrier function and a highmoisturizing function may be recovered. Therefore, a moisturizer can beobtained by incorporating the compound represented by the above Formula(1) therein. It has not been known hitherto that the compoundrepresented by the above Formula (1) has a function to enhance ceramideproduction at all, and this is a new discovery found by the inventors ofthe present invention.

In the present invention, the compound represented by the above Formula(1) may be directly used as a ceramide production enhancer.Alternatively, the compound may also be used as a formulation preparedby adding thereto various additives. For example, appropriate liquid orsolid excipients or bulking agents such as titanium oxide, calciumcarbonate, distilled water, lactose and starch, may be added to thecompound, and the resulting mixture may be used as the ceramideproduction enhancer.

In the case of preparing a composition, the amount of the compoundrepresented by the above Formula (1) in the ceramide production promoteris not particularly limited, but it is preferable that the compoundrepresented by the above Formula (1) be contained in an amount of0.00001 to 20% by mass, and more preferably 0.0001 to 10% by mass.

In the present invention, the compound represented by the above Formula(1) may be directly used as a moisturizer. Alternatively, the compoundrepresented by the above Formula (1) is incorporated as an activeingredient, and conventionally used additives, other efficaciousingredients and the like may be incorporated to the extent that theeffects of the compound are not affected, to prepare the moisturizer.For example, a ceramide production enhancer that is already known, apseudo-ceramide, a natural ceramide, a ceramide saccharide and the likemay be incorporated together. Furthermore, an anti-skin aging agent, awhitening agent and the like may also be added together as theefficacious ingredients in addition to the ingredients havingmoisturizing effects.

There are no particular limitations on the ceramide production enhanceralready known, pseudo-ceramide and ceramide saccharide, and thosementioned as examples in the descriptions on the ceramide productionenhancer and moisturizer containing the plant extract as an activeingredient may be used.

In the case of preparing a composition, the amount of the compoundrepresented by the above Formula (1) in the moisturizer is notparticularly limited, but it is preferable that the compound representedby the above Formula (1) be contained in an amount of 0.00001 to 20% bymass, and more preferably 0.0001 to 10% by mass.

The moisturizer of the present invention is mostly applied to humanbeings or animals. This moisturizer encompasses all dosage forms thatcan be applied to the skin, nails, mucous membranes, hair and the likeof a human being or an animal. Examples of the dosage forms of themoisturizer of the present invention include ointments, lotions, creams,beauty essences, skin lotions, massage agents, packs, foundations,lipsticks, bath additives, shampoos, hair conditioners, hair tonics,tablets, capsules, absorbent articles such as sanitary products, andsheet-like products such as bottom wipes and wet tissues. Theformulation form of the moisturizer is also not limited, and variousformulation forms such as a liquid form, a solid form, an emulsion form,a paste form, a gel form, a powder form, a granule form, a pellet form,and a stick form may be used.

The ceramide production enhancer and moisturizer of the presentinvention can be applied to the applications such as food products,cosmetic materials and medicinal products.

In the case of using in the food product applications, the ceramideproduction enhancer and moisturizer can be prepared into generalbeverage and food products, as well as health beverage and foodproducts, cosmetic beverage and food products, specified health beverageand food products, beverage and food products for patients, and thelike, which are based on the concept of the effect of improving andmaintaining the moisturization capacity or barrier function of the skin,and optionally have their object displayed thereon.

There are no particular limitations on the form of the food products,and examples include beverages such as fruit juice beverages, milkbeverages, and tea beverages; confectionaries such as candies, drops,jellies, cookies, chocolates, cakes, yogurt, and chewing gums;seasonings, cooking oil, dairy products, bread and buns, noodles, andprocessed rice. Furthermore, the food products may also be cosmetic foodproducts and health food products in the form of tablets, capsules,granules, syrups and the like.

These beverages and food products can be prepared by, for example, usingappropriate combinations of additives such as sweeteners, colorants,antioxidants, vitamins, flavors and minerals, and raw materials of foodproducts such as proteins, lipids, saccharides, carbohydrates andvegetable fibers, incorporating the plant extract or the compoundrepresented by the above Formula (1) to this combination, and processingthe mixture into various food product forms according to routinemethods.

In the case of using in the cosmetic material applications, for example,the ceramide production enhancer and the moisturizer can be preparedinto the form of external preparations for skin. In the case of using asthe form of an external preparation for skin, the various additives andother efficacious ingredients described above can be appropriatelyadded, in addition to the plant extract or the compound represented bythe above Formula (1), and also, those various components that areconventionally used in external preparations for skin can beincorporated in accordance with the formulation form that is employed.Specific examples of the formulation form of the external preparationsfor skin include various formulation forms capable of being externallyapplied, such as cream, milky lotion, lotion, gel, ointment, paste,pack, and sheet-like products. When preparing into these formulationforms, for example, various oil agents, surfactants, gelling agents,antiseptics, antioxidants, solvents, alcohols, water, chelating agents,thickeners, ultraviolet absorbents, emulsion stabilizers, pH adjustingagents, pigments, and fragrances can be incorporated.

The content of the plant extract or the compound represented by theabove Formula (1) in the external preparation for skin is the same asthe amount of the plant extract or the compound represented by the aboveFormula (1) in the ceramide production enhancer and the moisturizerdescribed above.

The form of administration in the case of using in the applications ofmedicinal products may be, for example, any of oral administration bymeans of tablets, capsules, granules, powders, syrups and the like, andparenteral administration by means of injectable preparations, externalpreparations, suppositories, transdermal absorbents and the like. In thepreparation of the medicinal preparations, the ceramide productionenhancer of the present invention can be used alone, or can be used inappropriate combination with other pharmaceutically acceptableexcipients, binders, extending agents, disintegrants, surfactants,lubricating agents, dispersants, buffering agents, preservatives,flavors, fragrances, film-forming agents, carriers, diluents and thelike.

The contents of the plant extract or the compound represented by theabove Formula (1) in the preparations are, as a dry solid component,preferably 0.00001% to 20% by mass, and particularly preferably 0.0001%to 10% by mass.

Although the amount of intake or use in the case of using the ceramideproduction enhancer or moisturizer of the present invention as a foodproduct, a cosmetic material or a medicinal product, can beappropriately selected in accordance with the conditions such as theform, the age and gender of the intaker, usually, it is preferable totake in or use the plant extract or the compound represented by theabove Formula (1) in an amount of 0.001 mg to 1000 mg, and it isparticularly preferable to take in or use the extract or the compound inan amount of 0.01 mg to 100 mg, per day for an adult.

EXAMPLES

Hereinafter, the present invention is described more in detail withreference to Examples, but the present invention is not limited thereto.

Preparation Example 1 Preparation of Extract of Chenopodium hybridum

Was 40 g of the whole grass of Chenopodium hybridum (manufactured byShinwa Bussan Co., Ltd.) finely cut, and 400 mL of 50% ethanol was addedthereto. Then, extraction was carried out for 23 days under theconditions of standing at room temperature. Thereafter, the extractionwas filtered to obtain 291 mL of a Chenopodium hybridum extract. For theextract thus obtained, the evaporation residue was calculated by amethod described below, and the evaporation residue was found to be 1.73(w/v %).

<Calculation of Evaporation Residue>

Was 1000 μl of the Chenopodium hybridum extract was dried for 6 hours at105° C. (dryer: DRY Thermo Unit DTU-1C (manufactured by TaitecCorporation) was used), and thus, 17.3 mg of a dried product wasobtained. The evaporation residue of this extract was calculated by theformula: 17.3/1000×100=1.73 (w/v %). In the Preparation Examplesdescribed below, the evaporation residue of each extract were calculatedin the same manner.

Preparation Example 2 Preparation of Extract of Melia toosendan

Was 40 g of the fruits of Melia toosendan (manufactured by Shinwa BussanCo., Ltd.) finely cut, and 400 mL of 50% ethanol was added thereto.Then, extraction was carried out for 23 days under the conditions ofstanding at room temperature. Thereafter, the extract was filtered toobtain 328 mL of a Melia toosendan extract (evaporation residue 1.68(w/v %)).

Preparation Example 3 Preparation of Extract of Indigofera tinctoria

Was 40 g of the dried pigments of the leaves of Indigofera tinctoria(manufactured by Shinwa Bussan Co., Ltd. finely cut, and 400 mL of 50%ethanol was added thereto. Then, extraction was carried out for 23 daysunder the conditions of standing at room temperature. Thereafter, theextract was filtered to obtain 347 mL of a Indigofera tinctoria extract(evaporation residue 0.72 (w/v %)).

Preparation Example 4 Preparation of Extract of Cirsium japonicum

Was 40 g of the roots of Cirsium japonicum (manufactured by ShinwaBussan Co., Ltd. finely cut, and 400 mL of 50% ethanol was addedthereto. Then, extraction was carried out for 23 days under theconditions of standing at room temperature. Thereafter, the extract wasfiltered to obtain 272 mL of a Cirsium japonicum extract (evaporationresidue 0.9 (w/v %)).

Preparation Example 5 Preparation of Extract of Catalpa ovata

Was 40 g of the fruits of Catalpa ovata (manufactured by Shinwa BussanCo., Ltd. was finely cut, and 400 mL of 50% ethanol was added thereto.Then, extraction was carried out for 23 days under the conditions ofstanding at room temperature. Thereafter, the extract was filtered toobtain 332 mL of a Catalpa ovata extract (evaporation residue 1.39 (w/v%)).

Preparation Example 6 Preparation of Extract of Tagetes erecta

Was 40 g of the flowers of Tagetes erecta (manufactured by Shinwa BussanCo., Ltd. finely cut, and 400 mL of 50% ethanol was added thereto. Then,extraction was carried out for 23 days under the conditions of standingat room temperature. Thereafter, the extract was filtered to obtain 262mL of a Tagetes erecta extract (evaporation residue 2.86 (w/v %)).

Test Example 1 Verification of Ceramide Production Enhancing Effect

Normal human epidermal keratinocytes (trade name: NHEK(F), manufacturedby Kurabo Industries, Ltd.) were cultured under the conditions of 37° C.and 5% CO₂, in a culture medium (trade name: EpiLife-KG2, manufacturedby Kurabo Industries, Ltd.) using a culture plate.

Thereafter, the culture medium was exchanged with EpiLife-KG2 withoutgrowth factors such as epidermal growth factor, and a dilution preparedfrom each of the extracts prepared in the Preparation Examples describedabove, the concentration of which was adjusted to 1 w/v % in terms ofsolids content, or a control solution (50% ethanol) was added to theculture fluid in an amount of 0.1%.

The cells were cultured for 3 days, and then the respective cells werecollected from each well.

An organic phase, contained lipids extracted from the collected cells bythe Blight and Dyer method, was transferred into a glass tube, and wasdried to solid in nitrogen stream. Subsequently, the dried product wasredissolved in chloroform and methanol, and this was used as a lipidsample.

Further, 0.1N NaOH and a 1% aqueous SDS solution were added to the cellsfrom which lipids had been extracted, and the mixture was heated at 60°C. for 2 hours to thereby solubilize proteins. The mixture was cooled toroom temperature, and then 2N HCl was added for neutralization. Theamount of proteins was quantified by the BCA method.

The lipid sample thus prepared was developed two times in a horizontalposition by thin layer chromatography (TLC) usingchloroform:methanol:acetic acid=190:9:1. A copper sulfate solution wassprayed, followed by baking on a hot plate, to thereby detect ceramides.This was designated as the amount of ceramides.

The results are shown in FIG. 1. Meanwhile, the vertical axis of thegraph shown in FIG. 1 represents the relative values in the case wherethe amount of ceramides of the control solution-added group Wasdesignated as 1.

As is obvious from FIG. 1, in the systems to which extracts ofChenopodium hybridum, Melia toosendan, Indigofera tinctoria, Cirsiumjaponicum, Catalpa ovata, and Tagetes erecta were added, it wasrecognized that the amounts of ceramide increased as compared to thecontrol.

Therefore, it was found that the ceramide production enhancers of thepresent invention containing these plant extracts as active ingredients,can enhance ceramide production. Furthermore, since ceramidesparticipate in the maintenance of water holding function and barrierfunction of the skin, it was found from the results of FIG. 1 that theplant extracts of the present invention enhances the production ofceramides and have a moisturizing function.

Preparation Example 7 Isolation of Component Having an Activity toEnhance Ceramide Production

Eight hundred g of the fruits of Melia toosendan (Senrenshi,manufactured by Shinwa Bussan Co., Ltd.) were extracted with 8 L of 50%ethanol at 20 to 35° C. for 7 days, and the solvent was concentrated.Thus, 123.5 g of an extracted solid fraction was obtained. The obtainedextracted solid fraction was fractionated based on the enhancingactivity of ceramide production assayed according to the test exampledescribed below. Liquid-liquid distribution was carried out by usingwater and ethyl acetate, and the inhibitory activity was concentrated in20.78 g of the ethyl acetate layer (yield 16.8%). The ethyl acetatelayer was further fractionated by silica gel column chromatography, andthus Fraction (1) 7.49 g was obtained (yield 6.1%). Fraction (1) wasfurther fractionated using silica gel column chromatography, and thusFraction (2) 2.78 g was obtained (yield 2.3%). Subsequently, thistraction was fractionated using LH-20 (Sephadex (trade mark) LH20,manufactured by GE Healthcare Inc.), and thus Fraction (3) 1.28 g wasobtained (yield 1.0%). 340 mg of Fraction (3) was fractionated by HPLC,and thus Fraction (4) 164.8 mg was obtained (yield 0.48%). Furthermore,20 mg of Fraction (4) was fractionated by HPLC, and thus Fraction (5)1.4 mg was obtained (yield 0.03%)) Fraction (5) was subjected to astructure analysis using NMR. In the structure analysis based on NMR,toosendanin which is commercially available as a reagent (manufacturedAvachem Scientific LLC) was used for comparison. The results of thestructure analysis based on NMR are presented in Table 1.

As a result, the active component isolated from Melia toosendan was acompound having a structure shown in the following Table 1, and thiscompound was identified as toosendanin. In Table 1, the abbreviation Acrepresents an acetyl group.

TABLE 1 13C-NMR (ppm) 1H-NMR (ppm) Isolated Toosendanin IsolatedToosendanin component (reagent) component (reagent) 1 70.7 70.7 4.244.24 2 37.2 37.2 1.8 1.8 2.73 2.73 3 74.8 74.8 5.19 5.19 4 41.2 41.2 — —5 29.6 29.6 2.8 2.8 6 26.2 26.2 1.71 1.71 2 2 7 70.8 70.9 3.57 3.57 843.9 43.9 — — 9 50.1 50.1 4.7 4.7 10 42.9 42.9 — — 11 209.1 209.1 — — 1279.7 79.7 5.33 5.33 13 46.9 46.9 — — 14 73.6 73.6 — — 15 60 60 3.81 3.816 34.8 34.8 2.02 2.01 2.11 2.11 17 39.9 39.9 2.88 2.88 18 15.9 15.81.37 1.38 19 65.5 65.5 4.25 4.24 4.31 4.31 20 124.3 124.3 — — 21 142.1142.1 7.2 7.2 22 113 113 6.16 6.16 23 143.7 143.7 7.4 7.4 28 20 20 0.840.84 29 97.2 97.2 4.83 4.83 30 23.1 23.2 1.12 1.12 AcO 21.4 21.4 2.072.07 172.9 172.9 — — 20.9 20.9 1.94 1.95 172.2 172.2 — —

Test Example 2 Verification of Ceramide Production Enhancing Effect

Normal human epidermal keratinocytes (trade name: NHEK(F), manufacturedby Kurabo Industries, Ltd.) were cultured under the conditions of 37° C.and 5% CO₂, in a culture fluid (trade name: EpiLife-KG2, manufactured byKurabo Industries, Ltd.) using a culture plate.

Thereafter, the culture fluid was exchanged with EpiLife-KG2 from whichgrowth factors such as epidermal growth factor had been eliminated, anda solution in which concentration of toosendanin was adjusted to 1 mM(574 ppm), or a control solution (50% ethanol) was added to the culturefluid in an amount of 0.01%.

The cells were cultured for 3 days, and then the respective cells werecollected from each well.

An organic phase obtained by extracting lipids from the collected cellsby the Blight and Dyer method, was transferred into a glass tube, andwas dried to solid in nitrogen stream. Subsequently, the dried productwas redissolved in chloroform and methanol, and this was used as a lipidsample.

Further, 0.1N NaOH and a 1% aqueous SDS solution were added to the cellsfrom which lipids had been extracted, and the mixture was heated at 60°C. for 2 hours to thereby solubilize proteins. The mixture was cooled toroom temperature, and then 2N HCl was added for neutralization. Theamount of proteins was quantified by the BCA method.

The lipid sample thus prepared was developed two times in a horizontalposition by thin layer chromatography (TLC) usingchloroform:methanol:acetic acid 190:9:1. A copper sulfate solution wassprayed, followed by baking on a hot plate, to thereby detect ceramides.This was designated as the amount of ceramides.

The results are shown in Table 2. Meanwhile, the amounts of ceramidesshown in Table 2 indicate relative values in the case where the amountof ceramides of the control solution-added group was designated as 1.

Reference Example 1. Preparation of Extract of Eucalyptus

Forty g of the leaves of Eucalyptus globulus Labillardiere (manufacturedby Shinwa Bussan Co., Ltd. were finely cut, and 400 mL of 50% ethanolwas added thereto. Then, extraction was carried out for 7 days under theconditions of standing at room temperature. Thereafter, the extract wasfiltered to obtain 291 mL of a Eucalyptus globulus Labillardiere extract(evaporation residue 3.16% (w/v)).

2. Verification of Ceramide Production Enhancing Effect

The ceramide production enhancing effect was verified according to thesame procedures used in Test Example 2, using the Eucalyptus extractthus obtained. Meanwhile, the addition to the cells was carried out suchthat an extract, the concentration of which was adjusted to be 1% (w/v)in terms of solids content, was added in an amount of 0.001%.

The results are shown in Table 2. Meanwhile, the Eucalyptus extract hasbeen well known as a moisturizing component having a ceramide productionenhancing function.

TABLE 2 Amount of ceramide production (Amount of Concen- ceramideproduction of tration for control solution-added verification group = 1)Remarks Toosendanin 57.4 ppb 1.22 Present invention Eucalyptus  100 ppb1.24 Reference extract example

As is obvious from Table 2, in the system to which toosendanin wasadded, an increase in the amount of ceramide production was recognizedas compared to the control system. Thus, it was understood that theceramide production enhancer of the present invention containing thecompound represented by the above Formula (1) as an active ingredient,can enhance ceramide production.

Furthermore, since ceramides participate in the maintenance of themoisturizing function and barrier function of the skin, it can be seenfrom the results of Table 2 that the compound represented by the aboveFormula (1) enhances the production of ceramides and has a moisturizingfunction. That is, similar to the Eucalyptus extract (ReferenceExample), which is a known moisturizing component, the moisturizer ofthe present invention containing the compound represented by the aboveFormula (1) as an active ingredient, is an agent which enhances theproduction of ceramides and has a moisturizing function.

Prescription Example 1

Using the extracts obtained by the Preparation Examples 1 to 6 as activeingredients, a skin lotion, an O/W (oil-in-water) type milky lotion, aW/O (water-in-oil) type cream, a gel-type cosmetics, and a liquid bathadditive, each having the composition described below, were prepared byroutine methods.

1-1. Preparation of Skin Lotion 1

(Composition) (Amount: mass %) Extract of Chenopodium hybridum 3.00Plyethylene glycol 1.00 (trade name: PEG-1540, manufactured by SanyoChemical Industries, Ltd.) Polyoxyethylene(20) sorbitan 1.50 monolauricacid ester Glycerin 2.00 Paraben 0.10 Purified water remnant1-2. Preparation of Skin Lotion 2

(Composition) (Amount: mass %) Extract of Melia toosendan 3.00Plyethylene glycol 1.00 (trade name: PEG-1540, manufactured by SanyoChemical Industries, Ltd.) Polyoxyethylene(20) sorbitan monolauric acidester 1.50 Glycerin 2.00 Paraben 0.10 Purified water remnant2-1. Preparation of O/W Type Milky Lotion 1

(Composition) (Amount: mass %) Extract of Indigofera tinctoria 3.00Plyethylene glycol 1.00 (trade name: PEG-2000, manufactured by SanyoChemical Industries, Ltd.) Pullulan 0.40 (Product name: Pullulan PT-20,manufactured by Hayashibara Co., Ltd.) Cetyl alcohol 1.00 Petrolatum2.00 Scualane 6.00 Dimethylpolysiloxane 2.00 Glycerin 2.00Pseudo-ceramide 1.00 (N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide) Polyoxyethylene(10) monooleic acid ester1.00 Glycerol monostearic acid ester 1.00 Acidic heteropolysaccharidesderived from the callus of a plant (1 wt % aqueous solution of tuberosepolysaccharide) 2.00 Paraben 0.20 Purified water remnant2-2. Preparation of O/W Type Milky Lotion 2

(Composition) (Amount: mass %) Extract of Cirsium japonicum 3.00Plyethylene glycol 1.00 (trade name: PEG-2000, manufactured by SanyoChemical Industries, Ltd.) Pullulan 0.40 (Product name: Pullulan PT-20,manufactured by Hayashibara Co., Ltd.) Cetyl alcohol 1.00 Petrolatum2.00 Scualane 6.00 Dimethylpolysiloxane 2.00 Glycerin 2.00Pseudo-ceramide 1.00 (N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide) Polyoxyethylene(10) monooleic acid ester1.00 Glycerol monostearic acid ester 1.00 Acidic heteropolysaccharidesderived from the 2.00 callus of a plant (1 wt % aqueous solution oftuberose polysaccharide) Paraben 0.20 Purified water remnant3-1. Preparation of W/O Type Cream 1

(Composition) (Amount: mass %) Extract of Catalpa ovata 3.00 Alkylacrylate copolymer 1.30 (trade name: Yodosol GH810, manufactured byKanebo NSC, Ltd.) Polyvinylpyrrolidone 0.70 (trade name: Rubiscol K-90,manufactured by BASE Japan, Ltd.) Dimethylpolysiloxane 10.00methylphenylpolysiloxane 3.00 Octamethylcyclotetrasiloxane 12.00Polyoxyalkylene-modified silicone 5.00 1,3-butylene glycol 6.00Pseudo-ceramide 1.20 (N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide) Paraben 0.20 Fragrance minute amountPurified water remnant3-2. Preparation of W/O Type Cream 2

(Composition) (Amount: mass %) Extract of Tagetes erecta 3.00 Alkylacrylate copolymer 1.30 (trade name: Yodosol GH810, manufactured byKanebo NSC, Ltd.) Polyvinylpyrrolidone 0.70 (trade name: Rubiscol K-90,manufactured by BASE Japan, Ltd.) Dimethylpolysiloxane 10.00methylphenylpolysiloxane 3.00 Octamethylcyclotetrasiloxane 12.00Polyoxyalkylene-modified silicone 5.00 1,3-butylene glycol 6.00Pseudo-ceramide 1.20 (N-(3-hexadecyloxy-2-hydroxypropyI)-N-2-hydroxyethylhexadecanamide) Paraben 0.20 fragrance minute amountPurified water remnant4-1. Preparation of Gel-Type Cosmetics 1

(Composition) (Amount: mass %) Extract of Chenopodium hybridum 1.00Plyethylene glycol 0.50 (trade name: PEG-2000, manufactured by SanyoChemical Industries, Ltd.) Xanthane gum 0.20 (trade name: Neosoft XKK,manufactured by KOHJIN Co., Ltd.) Glycerin 3.00 Ethanol 3.00Carboxyvinyl polymer 0.50 potassium hydroxide 0.15 Polyoxyethylenehardened castor oil 1.00 Citric acid 0.80 Trisodium citrate 0.80 Nylonpowder 1.00 Paraben 0.10 Fragrance minute amount Purified water remnant

(Composition) (Amount: mass %) Extract of Melia toosendan 1.00Plyethylene glycol 0.50 (trade name: PEG-2000, manufactured by SanyoChemical Industries, Ltd.) Xanthane gum 0.20 (trade name: Neosoft XKK,manufactured by KOHJIN Co., Ltd.) Glycerin 3.00 Ethanol 3.00Carboxyvinyl polymer 0.50 potassium hydroxide 0.15 Polyoxyethylenehardened castor oil 1.00 Citric acid 0.80 Trisodium citrate 0.80 Nylonpowder 1.00 Paraben 0.10 Fragrance minute amount Purified water remnant5-1. Preparation of Liquid Bath Additive 1

(Composition) (Amount: mass %) Extract of Indigofera tinctoria 3.00Pseudo-ceramide 0.10 (N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide) Isopropyl myristate 15.00Polyoxyethylene(12) oleyl ether 10.00 Polyoxyethylene(6) oleic acidester 6.00 Acidic heteropolysaccharides derived from 2.00 the callus ofa plant (1 wt % aqueous solution of tuberose polysaccharide) Paraben0.20 Fragrance minute amount liquid paraffin remnant5-2. Preparation of Liquid Bath Additive 2

(Composition) (Amount: mass %) Extract of Cirsium japonicum 3.00Pseudo-ceramide 0.10 (N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide) Isopropyl myristate 15.00Polyoxyethylene(12) oleil ether 10.00 Polyoxyethylene(6) oleil ether6.00 Acidic heteropolysaccharides derived from 2.00 the callus of aplant (1 wt % aqueous solution of tuberose polysaccharide) Paraben 0.30Fragrance minute amount liquid paraffin remnant

Prescription Example 2

A skin lotion, an O/W (oil-in-water) type milky lotion, a W/O(water-in-oil) type cream, a gel-type cosmetics, a liquid bath additiveand a food product in a tablet form, each having the compositiondescribed below, were prepared using toosendanin as an activeingredient, by routine methods.

1. Preparation of Lotion

(Composition) (Amount: mass %) Toosendanin (manufactured by AvaChem 0.05Scientific LLC) Plyethylene glycol 1.00 (trade name: PEG-1540,manufactured by Sanyo Chemical Industries, Ltd.) Polyoxyethylene(20)sorbitan monolauric acid ester 1.50 Glycerin 2.00 Paraben 0.10 Purifiedwater remnant2. Preparation of O/W Type Milky Lotion

(Composition) (Amount: mass %) Toosendanin (manufactured by AvaChem 1.00Scientific LLC) Plyethylene glycol 1.00 (trade name: PEG-2000,manufactured by Sanyo Chemical Industries, Ltd.) Pullulan 0.40 (Productname: Pullulan PT-20, manufactured by Hayashibara Co., Ltd.) Cetylalcohol 1.00 Petrolatum 2.00 Scualane 6.00 Dimethylpolysiloxane 2.00Glycerin 2.00 Pseudo-ceramide 1.00(N-(3-hexadecyloxy-2-hydroxypropyl)-N- 2-hydroxyethylhexadecanamide)Polyoxyethylene(10) monooleic acid ester 1.00 Glycerol monostearic acidester 1.00 Acidic heteropolysaccharides derived 2.00 from the callus ofa plant (1 wt % aqueous solution of tuberose polysaccharide) Paraben0.20 Purified water remnant3. Preparation of W/O Type Cream

(Composition) (Amount: mass %) Toosendanin (manufactured by AvaChem 3.00Scientific LLC) Alkyl acrylate copolymer 1.30 (trade name: YodosolGH810, manufactured by Kanebo NSC, Ltd.) Polyvinylpyrrolidone 0.70(trade name: Rubiscol K-90, manufactured by BASE Japan, Ltd.)Dimethylpolysiloxane 10.00 methylphenylpolysiloxane 3.00Octamethylcyclotetrasiloxane 12.00 Polyoxyalkylene-modified silicone5.00 1,3-butylene glycol 6.00 Pseudo-ceramide 1.20(N-(3-hexadecyloxy-2-hydroxypropyl)-N- 2-hydroxyethylhexadecanamide)Paraben 0.20 Fragrance minute amount Purified water remnant4. Preparation of Gel Type Cosmetics

(Composition) (Amount: mass %) Toosendanin (manufactured by 0.50 AvaChemScientific LLC) Plyethylene glycol 0.50 (trade name: PEG-2000,manufactured by Sanyo Chemical Industries, Ltd.) Xanthane gum 0.20(trade name: Neosoft XKK, manufactured by KOHJIN Co., Ltd.) Glycerin3.00 Ethanol 3.00 Carboxyvinyl polymer 0.50 potassium hydroxide 0.15Polyoxyethylene hardened castor oil 1.00 Citric acid 0.80 Trisodiumcitrate 0.80 Nylon powder 1.00 Paraben 0.10 Fragrance minute amountPurified water remnant5. Preparation of Liquid Bath Additive

(Composition) (Amount: mass %) Toosendanin (manufactured by AvaChem 0.01Scientific LLC) Pseudo-ceramide 0.10(N-(3-hexadecyloxy-2-hydroxypropyl)-N-2- hydroxyethylhexadecanamide)Isopropyl myristate 15.00 Polyoxyethylene(12) oleyl ether 10.00Polyoxyethylene(6) oleic acid ester 6.00 Acidic heteropolysaccharidesderived 2.00 from the callus of a plant (1 wt % aqueous solution oftuberose polysaccharide) Paraben 0.30 Fragrance minute amount liquidparaffin remnant6. Preparation of Food

Each material is mixed according to the composition described below, andform them into tablet.

(Composition) (Amount: mass %) Toosendanin (manufactured by AvaChem 1.0Scientific LLC) Crystalline cellulose 89.0 Whey calcium remnant

INDUSTRIAL APPLICABILITY

The ceramide production enhancer and the moisturizer of the presentinvention have functions to enhance ceramide production. Therefore, thepresent invention can be utilized in the fields of cosmetics, functionalfoods, medicinal products and medical treatments.

Having described our invention as related to the present embodiments, itis our intention that the invention not be limited by any of the detailsof the description, unless otherwise specified, but rather be construedbroadly within its spirit and scope as set out in the accompanyingclaims.

This application claims priority on Patent Application No. 2009-231847filed in Japan on Oct. 5, 2009 and Patent Application No. 2010-103651filed in Japan on Apr. 28, 2010, which are entirely herein incorporatedby reference.

The invention claimed is:
 1. A method of increasing the amount ofceramide in dry human skin, comprising applying an extract of Meliatoosendan to dry human skin that is need of an increase in the amount ofceramide, and increasing the amount of ceramide in said skin as a resultof said applying, wherein the extract of Melia toosendan is an extractof the fruit or seed of said Melia toosendan.
 2. The method of claim 1,wherein said extract is an extract of the fruit of Melia toosendan. 3.The method of claim 1, wherein the dry skin in need of the increase inceramide production is characterized by a decreased amount of ceramidein the stratum corneum as compared to skin that is not dry.
 4. Themethod of claim 1, wherein said extract is an extract of the seed ofMelia toosendan.
 5. The method of claim 1, wherein the extract is awater, ethanol or aqueous ethanol extract.
 6. The method of claim 5,wherein the extract is an aqueous ethanol extract.
 7. A method ofmoisturizing dry human skin by increasing the amount of ceramide in theskin, comprising applying an extract of Melia toosendan to dry humanskin that is in need of moisturizing, increasing the amount of ceramidein said skin as a result of said applying, and moisturizing said skin asa result of said increasing of the amount of said ceramide, wherein theextract of Melia toosendan is an extract of the fruit or seed of saidMelia toosendan.
 8. The method of claim 7, wherein said extract is anextract of the fruit of Melia toosendan.
 9. The method of claim 7,wherein the dry skin in need of moisturizing is characterized by adecreased amount of ceramide in the stratum corneum as compared to skinthat is not dry.
 10. The method of claim 7, wherein said extract is anextract of the seed of Melia toosendan.
 11. The method of claim 7,wherein the extract is a water, ethanol or aqueous ethanol extract. 12.The method of claim 11, wherein the extract is an aqueous ethanolextract.
 13. A method of increasing the amount of ceramide in dry humanskin, comprising (a) applying an extract of the fruit or seed of Meliatoosendan to dry human skin that is in need of an increase in the amountof ceramide, wherein the dry skin in which the amount of ceramide is tobe increased is characterized by a decreased amount of ceramide in thestratum corneum as compared to skin that is not dry, wherein the extractis a water, ethanol or aqueous ethanol extract, and (b) increasing theamount of ceramide in said dry skin as a result of the applying.
 14. Amethod of moisturizing dry human skin by increasing the amount ofceramide, comprising (a) applying an extract of the fruit or seed ofMelia toosendan to dry human skin that is in need of being moisturizedand is in need of an increase in the amount of ceramide in the skin,wherein the dry skin that is in need of an increase in the amount ofceramide is characterized by a decreased amount of ceramide in thestratum corneum as compared to skin that is not dry, wherein the extractis a water, ethanol or aqueous ethanol extract, (b) increasing theamount of ceramide in said skin as a result of the applying; and (c)moisturizing said dry skin as a result of said increasing of the amountof said ceramide.